Use of carboxylic acids having a sulphur function for promoting skin exfoliation or stimulating epidermal regeneration

ABSTRACT

PCT No. PCT/FR96/01658 Sec. 371 Date Apr. 29, 1998 Sec. 102(e) Date Apr. 29, 1998 PCT Filed Oct. 23, 1996 PCT Pub. No. WO97/16165 PCT Pub. Date May 9, 1997The use of carboxylic acids having a thioether function, a sulphoxide function or a sulphone function in or for making a cosmetic or dematological composition for promoting skin exfoliation and/or stimulating epidermal regeneration, is disclosed. The use of said composition for controlling intrinsic and extrinsic skin ageing, and a non-therapeutic skin treatment method useful for skin exfoliation, are also disclosed.

This application is a 371 of PCT/FR96/01658 filed Oct. 23, 1996.

The invention relates to the use of carboxylic acids carrying athioether function, a sulphoxide function or a sulphone function, in orfor the production of a cosmetic and/or dermatological composition forpromoting skin desquamation and/or combating intrinsic and extrinsicskin ageing. It also relates to a non-therapeutic skin treatment processfor desquamating the skin as well as to a treatment process forcutaneous ageing.

Cutaneous ageing resulting from effects of intrinsic or extrinsicfactors on the skin is shown by the appearance of wrinkles and lines,and the yellowing of the skin which develops a blotchy look accompaniedby the appearance of pigmentary spots, by the disorganization of theelastin and collagen fibres causing a loss of elasticity, of supplenessand of firmness and by the appearance of telangiectases.

Some of these signs of ageing are more particularly connected withintrinsic or physiological ageing, that is to say to "normal" ageingconnected with age, although others are more specific for extrinsicageing, that is to say ageing generally caused by the environment; moreparticularly photo-ageing due to exposure to the sun, to light or to anyother radiation.

The invention is concerned with intrinsic or physiological ageing aswell as with extrinsic ageing.

The changes in the skin due to intrinsic ageing are the consequence of agenetically programmed senescence in which endogenous factors intervene.This intrinsic ageing causes, especially, a slowing down of the renewalof the cells of the skin, which is essentially reflected by theappearance of clinical changes such as the reduction in the subcutaneousadipose tissue and the appearance of fine wrinkles or lines, and byhistopathological changes such as an increase in the number and thethickness of the elastic fibres, a loss of vertical fibres in themembrane of the elastic tissue, and the presence of large irregularfibroblasts in the cells of this elastic tissue.

In contrast, extrinsic ageing results in clinical alterations such asthick wrinkles and the formation of a flabby and tanned skin, and inhistopathological changes such as excessive accumulation of elasticmatter in the upper dermis and degeneration of the collagen fibres.

Various agents intended for combating cutaneous ageing are known in theprior art.

Thus, the patent U.S. Pat. No. 4,603,146 describes the use of retinoicacid and of its derivatives in cosmetic compositions, for the purpose ofcombating cutaneous ageing. However, many patents and publications (see,for example, the application EP-A-0413528) as well as numerouscommercial cosmetic compositions teach the use of α-hydroxy acids suchas lactic acid, glycolic acid or alternatively citric acid for treatingcutaneous ageing.

Finally, β-hydroxy acids and more especially salicylic acid as well asits derivatives are known for their desquamating properties (see thedocuments WO-A-93/10756 and U.S. Pat. No. 4,767,750).

All these compounds have an action against ageing of the skin,consisting in desquamation, that is to say the elimination of "dead"cells situated at the surface of the stratum corneum. This desquamatingproperty is also called, often wrongly, a keratolytic property. However,these compounds also have secondary effects, which consist of stinging,pulling, heating and redness, which are unpleasant for the user.

It is thus seen that the need exists for anti-ageing agents having anaction which is at least as effective as that of the compounds of theprior art, but does not have their disadvantages.

The Applicant has unexpectedly found that the topical application ofcertain carboxylic acids carrying a thioether function, a sulphoxidefunction or a sulphone function, makes it possible to desquamate theskin as well as to stimulate epidermal cell renewal and epidermalrepair.

Of course, carboxylic acids carrying a thioether function, a sulphoxidefunction or a sulphone function are already known in the cosmetic fieldin topical compositions for improving the elasticity of the skin (seethe document EP-A-0576287). However, nobody to date has envisaged orsuggested using these acids for the desquamation of the skin, thestimulation of epidermal renewal and the treatment of cutaneous ageing.

Consequently, a subject of the present invention is the use ofcarboxylic acids carrying a thioether function, a sulphoxide function ora sulphone function in the free state or at least partially neutralized,in or for the production of a cosmetic or dermatological composition forpromoting desquamation of the skin and/or stimulating epidermal renewal.

A subject of the present invention is likewise the use of carboxylicacids carrying a thioether function, a sulphoxide function or a sulphonefunction in the free state or at least partially neutralized, in or forthe production of a cosmetic or dermatological composition asanti-ageing agent, especially for combating wrinkles and/or lines and/oractinic spots and/or cutaneous dyschromias and/or dermitis and/orcicatrices.

A subject of the invention is more particularly the use of at least onecarboxylic acid carrying a thioether function, a sulphoxide function ora sulphone function, in the free state or at least partiallyneutralized, in or for the production of a cosmetic or dermatologicalcomposition for promoting desquamation of the skin and/or stimulatingepidermal renewal, this acid corresponding to one of the followingformulae (I), (II) or (III): ##STR1## in which n₁ is an integer of avalue ranging from 1 to 10, p₁ and q₁, which are identical or different,are 0, 1 or 2, n₂ is an integer of a value ranging from 0 to 5, p₂ is 0,1 or 2, q₂ is 0, 1, 2 or 3, m₂ is an integer of a value ranging from 0to 10, r₂ is 0 or 1, q₂ and n₂ never both being zero simultaneously,

R₁₁ and R'₁₁, which are identical or different, are a radical chosenfrom the group formed by: ##STR2## in which R₁₂ and R₁₃, which areidentical or different, are chosen from the group formed by the hydrogenatom and C₁ -C₈ linear or branched alkyl or alkenyl radicals; R₁₄ ischosen from the group formed by the hydrogen atom, linear or branched C₁-C₈ alkyl radicals, linear or branched C₁ -C₈ alkenyl radicals andlinear or branched C₁ -C₈ alkoxy radicals; R₁₅ and R₁₆ are chosen fromthe group formed by the hydrogen atom and linear or branched C₁ -C₈alkoxy radicals; R₂₁ and R₂₂ are chosen from the group formed by thehydrogen atom and linear or branched C₁ -C₆ alkoxy and alkenyl radicals,phenyl, C₁ -C₆ alkylcarboxylic and C₁ -C₆ alkenylcarboxylic acidradicals; R₂₃ is a C₁ -C₁₇ linear or branched alkyl or alkenyl radicalor an acyl radical --CO--R₂₄, where R₂₄ is a C₁ -C₁₇ linear or branchedalkyl or alkenyl radical; R₂₅ is chosen from the hydrogen atom, the C₁-C₆ linear or branched alkyl and alkenyl radicals, a C₁ -C₅alkyl-carboxylic acid radical, C₁ -C₅ alkenylcarboxylic acid radical andthe function --COOH; R₃₁ and R'₃₁ are chosen from the group formed fromthe radicals: ##STR3## and --CH₂ --CO₂ H

R₃₂ is a radical chosen from the group formed from:

i) --CH₃

ii) --CO₂ H ##STR4## such that R₃₄ is a radical chosen from: --CH₂ --CO₂H and --CO--CH₃

and R₃₅ is a radical chosen from : OH, OCH₃, OC(CH₃) ₃, OCH₂ CO₂ H

R₃₃ is a radical chosen from the group formed from:

the hydrogen atom, a C₁ -C₈ linear or branched alkyl or alkenyl radical,or R₃₂ and R₃₃ together form an alkane-diyl radical --(CH₂)m₃ --suchthat m₃ represents an integer of a value ranging from 3 to 5, or R₃₂ andR₃₃ together form an aralkanediyl radical ##STR5## such that n₃ is 3 or4.

The compounds which can be used according to the invention likewisecomprise the mono- and the disalts of the products described above, itbeing possible to choose these salts from the alkali metal salts,alkaline earth metal salts and the organic amine salts. By way ofexample, sodium salts, potassium, magnesium, calcium and strontiumsalts, ethanolamine, diethanolamine and triethanolamine salts, andlysine and arginine salts will be mentioned.

The desquamation of the skin is associated with a clinical improvementin the quality of the skin which becomes more radiant, less wrinkled andgenerally younger. In addition, the use of the acids described aboveallows imperfections in the skin such as spots, cutaneous dyschromias,dermitis, actinic lentigos, cicatrices and cicatricial pigmentations tobe treated.

Consequently, a subject of the invention is also the use of at least onecarboxylic acid carrying a thioether function, a sulphoxide function ora sulphone function and especially an acid corresponding to one of theformulae (I), (II) or (III) in the free state or at least partiallyneutralized, in or for the production of a cosmetic or dermatologicalcomposition as anti-ageing agent, especially for combating wrinklesand/or lines and/or actinic spots and/or cutaneous dyschromias and/ordermitis and/or cicatrices.

The Applicant has particularly noted, without this being completelyexplained, that the compounds have anti-ageing action which is at leastas effective as the compounds of the prior art and that this action ismilder in so far as no irritation is experienced and no redness isobserved when a cosmetic or dermatological composition containing themis applied to the skin.

Preferentially, the acids of the invention will be chosen from:

a) the compounds corresponding to the formula (I) in which

R₁₅ =R₁₆ =H, p₁ =q₁ and R₁₁ =R'₁₁,

b) the compounds corresponding to the formula (II) in which:

r₂ =1, R₂₃ =H, R₂₅ =--COOH and m=1 (cysteine derivatives) or m=2(homocysteine derivatives)

c) the compounds corresponding to the formula (III) in which:

R₃₂ is an aromatic radical, R₃₃ =H and R31=R'₃₁.

In particular, the acids of the invention are chosen from:

2,2'-dithiomethylenedibenzoic acid,

2,2'-dithioethylenedibenzoic acid,

2,2'-disulphinylethylenedibenzoic acid,

2,2'-(dithiopropane-1,3-diyl)dibenzoic acid,

2,2'-(dithiobutane-1,4-diyl)dibenzoic acid,

2,2'-(dithiopentane-1,5-diyl)dibenzoic acid,

2,2'-(dithiohexane-1,6-diyl)dibenzoic acid,

2,2'-(disulphinylhexane-1,6-diyl)dibenzoic acid,

α,α'-(dithiohexane-1,6-diyl)disuccinic acid,

2,2'-(dithiooctane-1,8-diyl)dibenzoic acid,

2,2'-(dithiodecane-1,10-diyl)dibenzoic acid,

α,α'-(dithiodecane-1,10-diyl)disuccinic acid,

α,α'-dithiomethylenediacetic acid,

α,α'-dithioethylenediacetic acid,

α,α'-disulphinylethylenediacetic acid,

α,α'-disulphonylethylenediacetic acid,

α,α'-(dithiohexane-1,6-diyl)diacetic acid,

α,α'-(disulphinylhexane-1,6-diyl)diacetic acid,

α,α'-(disulphonylhexane-1,6-diyl)diacetic acid,

α,α'-(dithiodecane-1,10-diyl)diacetic acid,

α,α'-(disulphinyldecane-1,10-diyl)diacetic acid,

α,α'-(disulphonyldecane-1,10-diyl)diacetic acid,

S-(carboxymethyl)cysteine,

S-(carboxyethyl)cysteine,

S-(4-carboxybutyl)cysteine,

S-(carboxymethyl)sulphinylcysteine,

S-(carboxymethyl)sulphonylcysteine,

S-(1-carboxy-1-ethyl)cysteine,

S-(2-carboxy-2-propyl)cysteine,

α,α'-(p-methoxybenzylidenedithio)disuccinic acid,

α,α'-(benzylidenedithio)disuccinic acid,

α,α'-(piperonylidenedithio)disuccinic acid,

α,α'-(vanillylidenedithio)disuccinic acid,

α,α'-(veratrylidenedithio)disuccinic acid,

α,α'-(4-butoxy-3-methoxybenzylidenedithio)disuccinic acid,

α,α'-(4-carboxymethyloxy-3-methoxybenzylidenedithio)-disuccinic acid,

α,α'-(p-methoxybenzylidenedithio)diacetic acid,

α,α'-(benzylidenedithio)diacetic acid,

α,α'-(piperonylidenedithio)diacetic acid,

α,α'-(vanillylidenedithio)diacetic acid,

α,α'-(veratrylidenedithio)diacetic acid,

as well as their inorganic or organic base monosalts and disalts.

Preferably, according to the invention, S-carboxymethylcysteine as wellas its inorganic or organic base mono- and disalts will be used.

The preparation of the products used according to the invention is wellknown to the person skilled in the art:

For the synthesis of the products corresponding to the formula (I), itis possible to refer to the document FR-2447189 in which this synthesisis described with R₁₅ =R₁₆ =H. The same synthesis methods are used inthe cases where R₁₅ and R₁₆ are other radicals.

The synthesis of the products corresponding to the formula (II) with p₂=0 is described in the documents FR-1505874 and FR-1472021. When p₂ =1,2, the products corresponding to the formula (II) are prepared startingfrom corresponding thioethers by an oxidizing treatment according to themethods known to the person skilled in the art. It is possible, forexample, to refer to the methods of oxidation of thioethers tosulphoxides and to sulphones described by Jerry March in "AdvancedOrganic Chemistry", Wiley Interscience, 3rd Edition p. 1089.

The synthesis of the products corresponding to the formula (III) hasbeen described in the document FR-2468362.

In the compositions according to the invention, the acid or the mixtureof carboxylic acids carrying a thioether function, a sulphoxide functionor a sulphone function, and especially the products according to theformulae (I), (II) and (III), can be used in a quantity ranging from 0.2to 20% by weight with respect to the total weight of the composition andin particular in a quantity ranging from 0.5 to 10% and, better, from0.5 to 5% by weight with respect to the total weight of the composition.

The acids of the invention can be combined with other active agentsknown for their desquamating properties, such as hydroxy acids, α- orβ-keto acids, and retinoids. Such a combination allows the activeconcentration of the latter to be decreased on account of additiveeffects. It is thus possible to obtain a less irritant and less toxiccomposition as well as a composition which is more effective than thoseof the prior art using only these active compounds.

The hydroxy acids can be, for example, α-hydroxy acids or β-hydroxyacids, which can be linear, branched or cyclic, saturated orunsaturated. The hydrogen atoms of the carbon chain, in addition, can besubstituted by halogens, or halogenated, alkylated, acylated,acyloxylated, alkoxycarbonylated or alkoxylated radicals having from 2to 18 carbon atoms.

These hydroxy acids are especially glycolic, lactic, malic, tartaric andcitric acids and, generally speaking, are fruit acids,2-hydroxylalkanoic, mandelic and salicylic acids, as well as theiralkylated or acylated derivatives such as 5-n-octanoylsalicylic acid,5-n-dodecanoylsalicylic acid, 5-n-decanoyl-salicylic acid,5-n-octylsalicylic acid, 5- or 4-n-heptyloxysalicylic acid,2-hydroxy-3-methylbenzoic acid, or alternatively their alkoxylatedderivatives such as 2-hydroxy-3-methoxybenzoic acid.

The retinoids can especially be retinoic acid (all-trans or 13-cis) andits derivatives, retinol (vitamin A) and its esters such as retinolpalmitate, retinol acetate and retinol propionate as well as theirsalts, or alternatively retinal.

By way of example, hydroxy acids, the keto acids and the retinoids canbe used in the compositions according to the invention in a quantityrepresenting from 0.1 to 5% by weight of the total weight of thecomposition and, better, from 0.5 to 3%.

For the purpose of effectively combating photo-ageing, it isadditionally possible to add to the composition of the invention one ormore hydrophilic or lipophilic complementary solar filters, which areactive in the UVA and/or the UVB.

An in vitro test of efficacy of desquamation has been carried out onkeratinocytes using 5-n-octanoylsalicylic acid (compound 1),S-carboxymethylcysteine (compound 2), the bis(1-ethoxycarbonylethyl)ester of nonanedioic acid (compound 3), 2-acetoxy-5-octanoylbenzoic acid(compound 4) and 5-oxothiomorpholine-3-carboxylic acid (compound 5).

The principle of the test is based on the fact that desquamation inducesthe release of corneocytes. The greater the desquamation power of theproduct tested, the greater the number of corneocytes released.

The protocol of the test was as follows:

keratinocytes were obtained from skin biopsies by separation of theepidermis, dissociated by enzymatic action with trypsin and cultured ata concentration of 2×10⁻⁵ cells/ml. Growth and differentiation of thekeratinocytes were obtained by culture for 10 to 20 days in a specificmedium.

Then, after removal of the culture medium, the product to be tested wasadded and the activity of the product was evaluated. To do this, twosamples were taken at T₀ and T₆₀, that is to say before the addition ofthe product and 60 minutes after this addition, and the samples thustaken were analysed in a flow cytometer in order to count the populationof corneocytes. The corneocyte and keratinocyte populations aredifferentiated in the flow cytometer by treatment with Acridine Orangewhich is specific for the DNA of the cells and which binds to thenucleus of the cells and thus exclusively reveals the presence of thekeratinocytes.

The cell detachment index is determined by the difference between T₆₀and T₀.

The same measurement was carried out for a control not containingproduct to be tested because the experiment inevitably causes theliberation of corneocytes, even in the absence of active agent. Thevariation in the control arbitrarily fixed the standard of 100%.

The results are collated in the table below:

    __________________________________________________________________________    Control                                                                            Compound 1                                                                           Compound 2                                                                          Compound 3                                                                           Compound 4                                                                           Compound 5                                    __________________________________________________________________________    0%   106%   121%  59%    inactive                                                                             inactive                                      __________________________________________________________________________

These results show clearly that S-carboxymethylcysteine, at aconcentration equal to that of 5-n-octanoylsalicylic acid which is knownas being a powerful desquamating active agent, is much more active thanthe latter, and that the other compounds have weaker activities thanthat of S-carboxymethylcysteine.

A further subject of the invention is a non-therapeutic process fortreatment of the skin intended for the desquamation of the skin,consisting in applying to the skin a composition containing at least onecarboxylic acid carrying a thioether function, a sulphoxide function ora sulphone function and especially an acid corresponding to one of theformulae (I), (II) or (III), in the free state or partially neutralized,in a cosmetically and/or dermatologically acceptable medium.

Another subject of the invention is a process for cosmetic ordermatological treatment of the ageing of the skin, consisting inapplying to the skin a composition containing at least one acid such asdefined above, in a cosmetically and/or dermatologically acceptablemedium.

The composition of the invention contains a cosmetically ordermatologically acceptable medium, that is to say a medium compatiblewith the skin, the nails, the mucous membranes, the tissues and thehair. The composition containing the acid carrying a thioether function,a sulphoxide function or a sulphone function can be applied topically tothe face, the neck, the hair, the mucous membranes and the nails or anyother cutaneous region of the body.

The compositions according to the invention can be present in all of theforms appropriate for topical application, especially in the form ofaqueous, aqueous/alcoholic or oily solutions, of dispersions of thelotion or serum type, of aqueous, anhydrous or oily gels, of emulsionsof liquid or semi-liquid consistency of the milk type, obtained bydispersion of a fatty phase in an aqueous phase (O/W) or conversely(W/O), of suspensions or emulsions of soft, semi-solid or solidconsistency of the cream or gel type, of microemulsions or alternativelyof microcapsules, of microparticles or of vesicular dispersions of ionicand/or non-Ionic type. These compositions are prepared according to theusual methods.

They can likewise be used for the hair in the form of aqueous, alcoholicor aqueous/alcoholic solutions, or in the form of creams, of gels, ofemulsions, of foams or alternatively in the form of aerosol compositionslikewise containing a propellant under pressure.

The quantities of the different constituents of the compositionsaccording to the invention are those conventionally used in the fieldsunder consideration.

These compositions especially form protection, treatment or care creamsfor the face, for the hands or for the body, protection or care bodymilks, lotions, gels or foams for the care of the skin and mucousmembranes or for cleansing the skin.

The compositions can likewise consist of solid preparations formingsoaps or cleansing bars.

When the composition of the invention is an emulsion, the proportion ofthe fatty phase can range from 5% to 80% by weight, and preferably from5% to 50% by weight with respect to the total weight of the composition.The oils, the emulsifiers and the co-emulsifiers used in the compositionin emulsion form are chosen from those conventionally used in thecosmetic or dermatological field. The emulsifier and the co-emulsifierare present, in the composition, in a proportion ranging from 0.3% to30% by weight and preferably from 0.5 to 20% by weight with respect tothe total weight of the composition. The emulsion can, in addition,contain lipid vesicles.

When the composition is an oily solution or an oily gel, the quantity ofoil can range up to more than 90% by weight of the total weight of thecomposition.

In a known manner, the composition of the invention can likewise containadjuvants customary in the cosmetic and dermatological fields, such ashydrophilic or lipophilic gelling agents, hydrophilic or lipophilicactive agents, preservatives, antioxidants, solvents, perfumes,sequestering agents, fillers and colouring materials. The quantities ofthese different adjuvants are those conventionally used in the fieldsunder consideration, for example from 0.01% to 20% of the total weightof the composition. These adjuvants, according to their nature, can beintroduced into the fatty phase, into the aqueous phase and/or intolipid spherules.

As oils which can be used in the invention, mention may be made ofmineral oils (liquid petrolatum), vegetable oils (karite oil, sweetalmond oil), animal oils, synthetic oils, silicone oils (cyclomethicone)and fluorinated oils (perfluoropolyethers). It is also possible to use,as fatty materials, fatty alcohols, fatty acids (stearic acid), or waxes(paraffin, carnauba, beeswax).

As emulsifiers which can be used in the invention, mention may be madeof Polysorbate 60 and sorbitan stearate sold respectively under thetrade names Tween 60 and Span 60 by the company ICI. It is also possibleto use PEG 20 stearate, marketed by the company ICI under the brandMYRJ.

As solvents which can be used in the invention, mention may be made oflower alcohols, especially ethanol and isopropanol, and propyleneglycol.

As hydrophilic gelling agents, mention may be made of carboxyvinylpolymers (carbomer), acrylic copolymers such as acrylate/alkylacrylatecopolymers, polyacrylamides, polysaccharides such ashydroxypropylcellulose, natural gums (xanthan) and clays, and, aslipophilic gelling agents, mention may be made of modified clays, suchas bentones, metallic salts of fatty acids such as aluminium stearates,hydrophobic silica, polyethylenes and ethylcellulose.

As hydrophilic active agents, proteins or protein hydrolysates, aminoacids, polyols, urea, allantoin, sugars and sugar derivatives,water-soluble vitamins, starch, bacterial or vegetable extracts,especially of Aloe Vera, or antiseptics.

As lipophilic active agents, it is possible to use tocopherol (vitaminE) and its derivatives, essential fatty acids, ceramides or essentialoils.

It is possible, inter alia, to combine the acids with active agentsintended especially for the prevention and/or for the treatment ofcutaneous ailments. Among these active agents, it is possible to mentionby way of example:

agents modulating cutaneous differentiation and/or proliferation and/orpigmentation, such as vitamin D and its derivatives, oestrogens such asoestradiol, kojic acid, or hydroquinone;

anti-free radical agents, such as α-tocopherol or its esters, superoxidedismutases, certain metal chelating agents or ascorbic acid and itsesters.

It is possible, in addition, to combine with the acids of the inventionantagonists of substance P and/or of CGRP (Calcitonin Gene-RelatedPeptide or peptide linked to the calcitonin gene) such as Iris Pallidaand strontium salts, especially the chlorides and the nitrates ofstrontium, or of antagonists of substance P and/or of CGRP such as thosedescribed in the French Patent Applications filed in the name of theApplicant under the numbers 9405537 and 9500900. Such a combinationallows a perfect tolerance of these compositions to be guaranteed, evenby very sensitive skins.

The cosmetic or dermatological treatment process of the invention can becarried out, especially, by applying the hygienic, cosmetic ordermatological compositions such as those defined above according to thetechnique of use customary for these compositions. For example:application of creams, of gels, of serums, of ointments, of lotions orof milks to the skin, the scalp, the nails and/or the mucuous membranes.

The following examples illustrate the invention. In these examples, theproportions indicated are percentages by weight.

EXAMPLE 1

Stabilizing Lotion

    ______________________________________                                        S-carboxymethylcysteine  2%                                                   Bactericide              0.1%                                                 Triethanolamine          1.7%                                                 Sequestering agent       0.1%                                                 Transcutol (Gattefosse)  5%                                                   Ethanol                 10.6%                                                 Water                   80.5%                                                 ______________________________________                                    

A lotion is obtained which, applied daily to the skin of the face,allows an improvement in the suppleness and in the elasticity of thetreated skin to be observed.

EXAMPLE 2

Colourless Cleansing Cream

    ______________________________________                                        Allantoin                0.1%                                                 S-carboxymethylcysteine  1%                                                   Glycerol stearate        1.2%                                                 Oils                    12%                                                   Wax                      2%                                                   Preservative             0.3%                                                 Antiseptic               0.2%                                                 Perfume                  0.4%                                                 Triethanolamine          0.8%                                                 Water                   qsp 100                                               PEG 20 stearate          6.6%                                                 Ethanol                  4.2%                                                 ______________________________________                                    

A cream is obtained which, on regular application, allows skin spots tobe reduced by desquamation.

EXAMPLE 3

Astringent Lotion

    ______________________________________                                        S-carboxymethylcysteine   2%                                                  Colourant                 0.00008%                                            Perfume                   0.08%                                               Ethyl alcohol            16.60%                                               Preservative              0.20%                                               Triethanolamine           1.5%                                                Sequestering agent        0.1%                                                Extra-light precipitated magnesium carbonate                                                            0.08%                                               Water                    qsp 100                                              Ethanol                  16.6%                                                ______________________________________                                    

Application of this solution under dermatological control allows a deepdesquamation of the horny layer to be obtained and, thus, the bringinginto play of an epidermal repair process, having as its finaltherapeutic effect an erasure of spots and dyschromias, a reduction inwrinkles and lines and an improvement in the clinical state of the skin,which takes on the appearance of a younger skin.

This application is made at a rate of one to three weekly sessions for 4to 6 weeks.

EXAMPLE 4

Astringent Lotion

This example differs from Example 3 by the addition of 0.25% ofstrontium nitrate. This formula is particularly suitable for thetreatment of sensitive skins.

What is claimed is:
 1. A method of desquamating skin and/or promotingepidermal renewal in skin, comprising applying to the skin an effectiveamount of at least one carboxylic acid and/or a salt thereof representedby formula (I) (II) or (III): ##STR6## wherein n is an integer of avalue ranging from 1 to 10,p₁ and q₁, which are identical or different,are 0, 1 or 2, n₂ is an integer of a value ranging from 0 to 5, p₂ is 0,1 or 2, q₂ is 0, 1 or 2, q₂ is 0, 1, 2 or 3, m₂ is an integer of a valueranging from 0 to 10, r₂ is 0 or 1, q₂ and n₂ never both being zerosimultaneously, R₁₁ and R'₁₁, which are identical or different, are aradical selected from the group consisting of ##STR7## wherein R₁₂ andR₁₃, which are identical or different, are selected from the groupconsisting of a hydrogen atom and C₁ -C₈ linear or branched alkyl oralkenyl radicals; R₁₄ is selected from the group consisting of ahydrogen atom, linear or branched C₁ -C₈ alkyl radicals, linear orbranched C₁ -C₈ alkenyl radicals and linear and branched C₁ -C₈ alkoxyradicals; R₁₅ and R₁₆ are selected from the group consisting of ahydrogen atom and linear or branched C₁ -C₈ alkoxy radicals; R₂₁ and R₂₂are selected from the group consisting of a hydrogen atom and linear orbranched C₁ -C₆ alkoxy and alkenyl radicals, phenyl, C₁ -C₆alkylcarboxylic and C₁ -C₆ alkenylcarboxylic acid radicals; R₂₃ is a C₁-C₁₇ linear or branched alkyl or alkenyl radical or an acyl radical--CO--R₂₄, where R₂₄ is a C₁ -C₁₇ linear or branched alkyl or alkenylradical; R₂₅ is selected from the group consisting of a hydrogen atom, aC₁ -C₆ linear or branched alkyl and alkenyl radical, a C₁ -C₅alkyl-carboxylic acid radical, C₁ -C₅ alkenylcarboxylic acid radical andthe function --COOH; R₃₁ and R'₃₁ are selected from the group consistingof ##STR8## R₃₂ is a radical selected from the group consisting of i)--CH₃ ii) --CO₂ H ##STR9## wherein R₃₄ is a radical selected from thegroup consisting of --CH₂ --CO₂ H and --CO--CH₃, and R₃₅ is a radicalselected from the group consisting of OH, OCH₃, OC(CH₃)₃, and OCH₂ CO₂H, R₃₃ is a radical selected from the group consisting of a hydrogenatom, a C₁ -C₆ linear or branched alkyl or alkenyl radical, or R₃₂ andR₃₃ together form an alkane diyl radical --(CH₂)m₃ -- wherein m₃represents an integer of a value ranging from 3 to 5, or R₃₂ and R₃₃together form an aralkanediyl radical represented by the formula##STR10## wherein n₃ is 3 or
 4. 2. The method of claim 1, which isdesquamating skin.
 3. The method of claim 1, which is promotingepidermal renewal in skin.
 4. The method of claim 1, wherein at least aportion of the carboxylic acid is in the form of a salt.
 5. The methodof claim 1, wherein the acids are selected from the group consistingof(a) compounds corresponding to formula (I) in which R₁₅ =R₁₆ =H, p₁=q₁ and R₁₁ =R'₁₁, (b) compounds corresponding to formula (II) in whichr₂ =1, R₂₃ =H, R₂₅ =--COOH and m=1 (cysteine derivatives) or m=2, and(c) compounds corresponding to formula (III) in which R₃₂ is an aromaticradical, R₃₃ =H and R₃₁ =R'₃₁.
 6. The method of claim 1, wherein theacid is selected from the group consistingof2,2'-dithiomethylenedibenzoic acid, 2,2'-dithioethylenedibenzoic acid,2,2'-disulphinylethylenedibenzoic acid,2,2'-(dithiopropane-1,3-diyl)dibenzoic acid,2,2'-(dithiobutane-1,4-diyl)dibenzoic acid,2,2'-(dithiopentane-1,5-diyl)dibenzoic acid,2,2'-(dithiohexane-1,6-diyl)dibenzoic acid,2,2'-(disulphinylhexane-1,6-diyl)dibenzoic acid,α,α'-(dithiohexane-1,6-diyl)disuccinic acid, 2.2'-(dithiooctane-1,8-diyl)dibenzoic acid,2,2'-(dithiodecane-1,10-diyl)dibenzoic acid, α,α'-(dithiodecane- 1,10-diyl )disuccinicacid, α,α'-dithiomethylenediacetic acid, α,α'-dithioethylenediaceticacid, α,α'-disulphinylethylenediacetic acid,α,α'-disulphonylethylenediacetic acid,α,α'-(dithiohexane-1,6-diyl)diacetic acid,α,α'-(disulphinylhexane-1,6-diyl)diacetic acid,α,α'-(disulphonylhexane-1,6-diyl)diacetic acid,α,α'-(dithiodecane-1,10-diyl)diacetic acid,α,a'-(disulphinyldecane-1,10-diyl)diacetic acid,α,α'-(disulphonyldecane-1,10-diyl)diacetic acid,S-(carboxymethyl)cysteine, S-(carboxyethyl)cysteine,S-(4-carboxybutyl)cysteine, S-(carboxymethyl)sulphinylcysteine,S-(carboxymethyl)sulphonylcysteine, S-(1-carboxy-1-ethyl)cysteine,S-(2-carboxy-2-propyl)cysteine,α,α'-(p-methoxybenzylidenedithio)disuccinic acid,α,α'-(benzylidenedithio)disuccinic acid,α,α'-(piperonylidenedithio)disuccinic acid,α,α'-(vanillylidenedithio)disuccinic acid,α,α'-(veratrylidenedithio)disuccinic acid,α,α'-(4-butoxy-3-methoxybenzylidenedithio)disuccinic acid,α,α'-(4-carboxymethyloxy-3-methoxybenzylidenedithio)disuccinic acid,α,α'-(p-methoxybenzylidenedithio)diacetic acid,α,α'-(benzylidenedithio)diacetic acid,α,α'-(piperonylidenedithio)diacetic acid,α,α'-(vanillylidenedithio)diacetic acid, andα,α'-(veratrylidenedithio)diacetic acid,or a salt thereof.
 7. The methodof claim 1, wherein the acid is S-carboxymethylcysteine or an ofinorganic or organic base mono- or disalt thereof.
 8. The method ofclaim 1, wherein the acid is applied to the skin as a topicallyacceptable composition, wherein the composition comprises from 0.2 to20% by weight of the acid, based on the total weight of the composition.9. The method of claim 8, wherein the composition comprises from 0.5 to5% by weight of the acid, based on the total weight of the composition.10. The method of claim 8, wherein the composition further comprises atleast one active agent selected from the group consisting of α- orβ-hydroxy acids, α- or β-keto acids, and retinoids.
 11. The method ofclaim 8, wherein the composition further comprises at least one activeagent selected from the group consisting of the glycolic, lactic, malic,tartaric, citric, 2-hydroxyalkanoic, mandelic or salicylic acids, and5-n-octanoylsalicylic acid.
 12. The method of claim 10, wherein thecomposition comprises from 0.1 to 5% by weight of the active agent,based on the total weight of the composition.
 13. The method of claim11, wherein the composition comprises from 0.1 to 5% by weight of theactive agent, based on the total weight of the composition.
 14. Themethod of claim 8, wherein the composition further comprises at leastone adjuvant selected from the group consisting of proteins or proteinhydrolysates, amino acids, polyols, urea, sugars and sugar derivatives,vitamins, starch, vegetable extracts, essential fatty acids, ceramides,and essential oils.
 15. The method of claim 8, wherein the compositionis an aqueous, oily or aqueous/alcoholic solution, a water-in-oil oroil-in-water emulsion, a microemulsion, an aqueous or anhydrous gel, aserum or dispersion of vesicles, of microcapsules or of microparticles.16. The method of claim 8, wherein the composition further comprises atleast one antagonist of substance P and/or of CGRP.
 17. The method ofclaim 16, wherein the antagonist is a strontium salt.
 18. The method ofclaim 1, wherein the carboxylic acid, or the salt thereof, has athioether function.
 19. The method of claim 1, wherein the carboxylicacid, or the salt thereof, has a sulphoxide function.
 20. The method ofclaim 1, wherein the carboxylic acid, or the salt thereof, has asulphone function.
 21. A method of treating cutaneous aging in skincomprising applying to the skin an effective amount of at least onecarboxylic acid and/or a salt thereof represented by formula (I) (II) or(III): ##STR11## wherein n is an integer of a value ranging from 1 to10,p₁ and q₁, which are identical or different, are 0, 1 or 2, n₂ is aninteger of a value ranging from 0 to 5, p₂ is 0, 1 or 2, q₂ is 0, 1 or2, q₂ is 0, 1, 2 or 3, m₂ is an integer of a value ranging from 0 to 10,r₂ is 1, q₂ and n₂ never both being zero simultaneously, R₁₁ and R'₁₁,which are identical or different, are a radical selected from the groupconsisting of ##STR12## wherein R₁₂ and R₁₃, which are identical ordifferent, are selected from the group consisting of a hydrogen atom andC₁ -C₈ linear or branched alkyl or alkenyl radicals; R₁₄ is selectedfrom the group consisting of a hydrogen atom, linear or branched C₁ -C₈alkyl radicals, linear or branched C₁ -C₈ alkenyl radicals and linearand branched C₁ -C₈ alkoxy radicals; R₁₅ and R₁₆ are selected from thegroup consisting of a hydrogen atom and linear or branched C₁ -C₈ alkoxyradicals; R₂₁ and R₂₂ are selected from the group consisting of ahydrogen atom and linear or branched C₁ -C₆ alkoxy and alkenyl radicals,phenyl, C₁ -C₆ alkylcarboxylic and C₁ -C₆ alkenylcarboxylic acidradicals; R₂₃ is a C₁ -C₁₇ linear or branched alkyl or alkenyl radicalor an acyl radical --CO--R₂₄, where R₂₄ is a C₁ -C₁₇ linear or branchedalkyl or alkenyl radical; R₂₅ is selected from the group consisting of ahydrogen atom, a C₁ -C₆ linear or branched alkyl and alkenyl radical, aC₁ -C₅ alkyl-carboxylic acid radical, C₁ -C₅ alkenylcarboxylic acidradical and the function --COOH; R₃₁ and R'₃₁ are selected from thegroup consisting of ##STR13## and

    --CH.sub.2 --CO.sub.2 H

R₃₂ is a radical selected from the group consisting ofi) --CH₃ ii) --CO₂H ##STR14## wherein R₃₄ is a radical selected from the group consistingof --CH₂ --CO₂ H and --CO--CH₃, and R₃₅ is a radical selected from thegroup consisting of OH, OCH₃, OC(CH₃)₃, and OCH₂ CO₂ H, R₃₃ is a radicalselected from the group consisting of a hydrogen atom, a C₁ -C₆ linearor branched alkyl or alkenyl radical, or R₃₂ and R₃₃ together form analkane diyl radical --(CH₂)m₃ -- wherein m₃ represents an integer of avalue ranging from 3 to 5, or R₃₂ and R₃₃ together form an aralkanediylradical represented by the formula ##STR15## wherein n₃ is 3 or
 4. 22.The method of claim 21, wherein the acids are selected from the groupconsisting of(a) compounds corresponding to formula (1) in which R₁₅=R₁₆ =H, p₁ =q₁ and R₁₁ =R'₁₁, (b) compounds corresponding to formula(II) in which r₂ =1, R₂₃ =H, R₂₅ =--COOH and m=1 (cysteine derivatives)or m=2, and (c) compounds corresponding to formula (III) in which R₃₂ isan aromatic radical, R₃₃ =H and R₃₁ =R'₃₁.
 23. The method of claim 21,wherein the acid is selected from the group consistingof2,2'-dithiomethylenedibenzoic acid, 2,2'-dithioethylenedibenzoic acid,2,2'-disulphinylethylenedibenzoic acid,2,2'-(dithiopropane-1,3-diyl)dibenzoic acid,2,2'-(dithiobutane-1,4-diyl)dibenzoic acid,2,2'-(dithiopentane-1,5-diyl)dibenzoic acid,2,2'-(dithiohexane-1,6-diyl)dibenzoic acid,2,2'-(disulphinylhexane-1,6-diyl)dibenzoic acid,α,α'-(dithiohexane-1,6-diyl)disuccinic acid, 2.2'-(dithiooctane-1,8-diyl)dibenzoicacid,2,2'-(dithiodecane-1,10-diyl)dibenzoic acid,α,α'-(dithiodecane-1,10-diyl)disuccinic acid,α,α'-dithiomethylenediacetic acid, α,α'-dithioethylenediacetic acid,α,α'-disulphinylethylenediacetic acid, α,α'-disulphonylethylenediaceticacid, α,α'-(dithiohexane-1,6-diyl)diacetic acid,α,α'-(disulphinylhexane-1,6-diyl)diacetic acid,α,α'-(disulphonylhexane-1,6-diyl)diacetic acid, α,α'-(dithiodecane-1,10-diyl)diacetic acid, α,α'-(disulphinyldecane- 1,10-diyl)diaceticacid, α,α'-(disulphonyldecane- 1,10-diyl)diacetic acid,S-(carboxymethyl)cysteine, S-(carboxyethyl)cysteine,S-(4-carboxybutyl)cysteine, S-(carboxymethyl)sulphinylcysteine,S-(carboxymethyl)sulphonylcysteine, S-(1-carboxy-1-ethyl)cysteine,S-(2-carboxy-2-propyl)cysteine,α,α'-(p-methoxybenzylidenedithio)disuccinic acid,α,α'-(benzylidenedithio)disuccinic acid,α,α'-(piperonylidenedithio)disuccinic acid,α,α'-(vanillylidenedithio)disuccinic acid,α,α'-(veratrylidenedithio)disuccinic acid,α,α'-(4-butoxy-3-methoxybenzylidenedithio)disuccinic acid,α,α'-(4-carboxymethyloxy-3-methoxybenzylidenedithio)disuccinic acid,α,α'-(p-methoxybenzylidenedithio)diacetic acid,α,α'-(benzylidenedithio)diacetic acid,α,α'-(piperonylidenedithio)diacetic acid,α,α'-(vanillylidenedithio)diacetic acid, andα,α'-(veratrylidenedithio)diacetic acid,or a salt thereof.
 24. Themethod of claim 21, wherein the acid is S-carboxymethylcysteine or aninorganic or organic base mono- or disalt thereof.
 25. The method ofclaim 21, wherein the acid is applied to the skin as a topicallyacceptable composition, wherein the composition comprises from 0.2 to20% by weight of the acid, based on the total weight of the composition.26. The method of claim 25, wherein the composition comprises from 0.5to 5% by weight of the acid, based on the total weight of thecomposition.
 27. The method of claim 25, wherein the composition furthercomprises at least one active agent selected from the group consistingof α- or β-hydroxy acids, α- or β-keto acids, and retinoids.
 28. Themethod of claim 25, wherein the composition further comprises at leastone active agent selected from the group consisting of the glycolic,lactic, malic, tartaric, citric, 2-hydroxyalkanoic, mandelic andsalicylic acids, and 5-n-octanoylsalicylic acid.
 29. The method of claim27, wherein the composition comprises 0.1 to 5% by weight of the activeagent, based on the total weight of the composition.
 30. The method ofclaim 28, wherein the composition comprises from 0.1 to 5% by weight ofthe active agent, based on the total weight of the composition.
 31. Themethod of claim 25, wherein the composition further comprises at leastone adjuvant selected from the group consisting of proteins and proteinhydrolysates, amino acids, polyols, urea, sugars and sugar derivatives,vitamins, starch, vegetable extracts, essential fatty acids, ceramides,and essential oils.
 32. The method of claim 25, wherein the compositionis an aqueous, oily or aqueous/alcoholic solution, a water-in-oil oroil-in-water emulsion, a microemulsion, an aqueous or anhydrous gel, aserum or dispersion of vesicles, of microcapsules or of microparticles.33. The method of claim 25, wherein the composition further comprises atleast one antagonist of substance P and/or of CGRP.
 34. The method ofclaim 33, wherein the antagonist is a strontium salt.
 35. The method ofclaim 21, wherein the carboxylic acid, or salt thereof, has a thioetherfunction.
 36. The method of claim 21, wherein the carboxylic acid, orthe salt thereof, has a sulphoxide function.
 37. The method of claim 21,wherein the carboxylic acid, or the salt thereof, has a sulphonefunction.